Is inclisiran (Leqvio) medically necessary for a patient with mixed hyperlipidemia, essential hypertension, atherosclerotic heart disease, and type 2 diabetes mellitus, with a current Low-Density Lipoprotein Cholesterol (LDL-C) level of 46 mg/dL, who has been taking ezetimibe (Zetia) for more than 3 months?

Inclisiran (Leqvio) is NOT Medically Necessary for This Patient

Based on the current clinical documentation, inclisiran does not meet medical necessity criteria because the patient's LDL-C is 46 mg/dL—well below the required threshold of ≥70 mg/dL for patients with ASCVD, and there is insufficient documentation of adequate statin trial duration or intolerance. 1, 2

Critical Deficiencies in Meeting CPB 1004 Criteria

LDL-C Level Does Not Support Continued Therapy

• The patient's current LDL-C of 46 mg/dL is significantly below the required threshold of ≥70 mg/dL for patients with clinical ASCVD, which is the primary criterion for inclisiran approval in this population 1, 2
• For patients with multiple ASCVD events or high-risk conditions, the threshold is ≥55 mg/dL—this patient still does not meet this lower threshold 2
• The 2024 International Lipid Expert Panel explicitly states that once LDL-C goals are achieved with well-tolerated therapy, treatment should NOT be de-escalated, but this applies to continuing existing therapy, not initiating new expensive therapy when goals are already met 3

Inadequate Documentation of Statin Trial

• The medical record shows ezetimibe (Zetia) use from a specific start date to end date, but there is NO clear documentation of:
  • Duration of high-intensity or maximally tolerated statin therapy (required: ≥3 months) 2
  • Specific statin intolerance symptoms or contraindications 2
  • Whether the patient is currently on any statin therapy 2
• The CPB 1004 criteria explicitly require either 3 months of maximally tolerated statin therapy OR documented contraindication/intolerance to statins 2

Treatment Algorithm Violation

• The American College of Cardiology recommends PCSK9 monoclonal antibodies (evolocumab, alirocumab) as the PREFERRED PCSK9 inhibitor class over inclisiran due to proven cardiovascular outcomes benefits in the FOURIER and ODYSSEY Outcomes trials 1
• Inclisiran lacks completed cardiovascular outcomes data until 2026-2027 (ORION-4 and VICTORION-2P trials pending) 1
• Inclisiran should be considered primarily in patients with demonstrated poor adherence to PCSK9 mAbs, adverse effects from both available PCSK9 mAbs, or inability to self-inject medications—none of which are documented in this case 1, 2

Appropriate Treatment Pathway for This Patient

If LDL-C Were Still Elevated (Which It Is Not)

• Step 1: Confirm patient is on maximally tolerated statin therapy for ≥3 months 1, 2
• Step 2: Add ezetimibe 10 mg daily if not already optimized 1
• Step 3: Reassess LDL-C after 4-12 weeks 3, 4
• Step 4: If LDL-C remains ≥70 mg/dL despite statin plus ezetimibe, add PCSK9 mAb (evolocumab or alirocumab) as preferred option 1
• Step 5: Consider inclisiran ONLY if PCSK9 mAb fails due to adherence issues, adverse effects from both available mAbs, or inability to self-inject 1, 2

Current Clinical Reality

• The patient has already achieved an LDL-C of 46 mg/dL, which is below the target of <55 mg/dL for very high-risk ASCVD patients and well below the <70 mg/dL threshold for standard ASCVD patients 3, 1
• There is no clinical rationale for adding expensive PCSK9 inhibitor therapy when LDL-C goals are already met 1, 2

Required Documentation for Reconsideration

To potentially justify inclisiran, the following MUST be documented:

• Current LDL-C level ≥70 mg/dL (or ≥55 mg/dL if multiple ASCVD events present) obtained within 4 weeks 2
• Clear documentation of ≥3 months of maximally tolerated statin therapy, including:
  • Specific statin name and dose 2
  • Duration of therapy 2
  • Reason for discontinuation if not currently on statin 2
• If claiming statin intolerance, documentation must include:
  • Specific symptoms experienced 2
  • Multiple statin trials attempted 2
  • Rechallenge attempts 2
• Documentation of why PCSK9 mAb (evolocumab or alirocumab) was not tried first or failed 1, 2

Common Pitfalls to Avoid

• Do not confuse "patient is on ezetimibe" with "patient has completed adequate statin trial"—these are separate requirements 2
• Do not assume that because a patient has severe ASCVD, they automatically qualify for inclisiran—specific LDL-C thresholds and treatment algorithm steps must be met 1, 2
• Do not initiate inclisiran as first-line PCSK9 inhibitor therapy—PCSK9 mAbs with proven cardiovascular outcomes data should be tried first unless specific contraindications exist 1
• Do not continue expensive therapies when LDL-C goals are already achieved with current regimen—this represents poor stewardship of healthcare resources without clinical benefit 1, 2

Bottom Line for This Authorization Request

The request for inclisiran J1306 should be DENIED based on:

1. Current LDL-C of 46 mg/dL does not meet the ≥70 mg/dL threshold required for ASCVD patients 1, 2
2. Inadequate documentation of required 3-month statin trial or documented statin intolerance 2
3. No documentation of PCSK9 mAb trial failure or contraindication 1, 2
4. Patient has already achieved guideline-recommended LDL-C goals with current therapy 3, 1

If the provider believes inclisiran is still indicated, they must submit updated documentation addressing all deficiencies listed above, particularly a current LDL-C level showing inadequate control (≥70 mg/dL) and complete statin therapy history. 2